17-6589759-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014804.3(KIAA0753):c.2786+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00418 in 1,571,708 control chromosomes in the GnomAD database, including 214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (112 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (102 hom.)
• Consequence: KIAA0753 NM_014804.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.158

Genes affected

KIAA0753 (HGNC:29110): (KIAA0753) This gene encodes a subunit of a protein complex that regulates ciliogenesis and cilia maintenance. The encoded protein has also been shown to regulate centriolar duplication. Mutations in this gene cause an orofaciodigital syndrome and a form of Joubert syndrome in human patients. [provided by RefSeq, May 2017]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 17-6589759-G-A is Benign according to our data. Variant chr17-6589759-G-A is described in ClinVar as [Benign]. Clinvar id is 1248546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA0753	NM_014804.3	c.2786+20C>T		intron_variant		ENST00000361413.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA0753	ENST00000361413.8	c.2786+20C>T		intron_variant		1	NM_014804.3	P1

Frequencies

GnomAD3 genomes AF: 0.0218 AC: 3318 AN: 152148 Hom.: 111 Cov.: 33

Gnomad AFR AF: 0.0745

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0104

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0187

GnomAD3 exomes AF: 0.00569 AC: 1271 AN: 223258 Hom.: 49 AF XY: 0.00417 AC XY: 507 AN XY: 121680

Gnomad AFR exome AF: 0.0748

Gnomad AMR exome AF: 0.00298

Gnomad ASJ exome AF: 0.00279

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000272

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000267

Gnomad OTH exome AF: 0.00434

GnomAD4 exome AF: 0.00228 AC: 3236 AN: 1419442 Hom.: 102 Cov.: 28 AF XY: 0.00195 AC XY: 1378 AN XY: 707044

Gnomad4 AFR exome AF: 0.0759

Gnomad4 AMR exome AF: 0.00420

Gnomad4 ASJ exome AF: 0.00257

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000209

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000240

Gnomad4 OTH exome AF: 0.00604

GnomAD4 genome AF: 0.0218 AC: 3326 AN: 152266 Hom.: 112 Cov.: 33 AF XY: 0.0211 AC XY: 1569 AN XY: 74456

Gnomad4 AFR AF: 0.0744

Gnomad4 AMR AF: 0.0104

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.0185

Alfa AF: 0.0118 Hom.: 11

Bravo AF: 0.0254

Asia WGS AF: 0.00924 AC: 32 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 05, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 28, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	7.0
Dann	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs74701712; hg19: chr17-6493079;